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transduction pathways in this manner by altering ion homeostasis (Stoyanovsky, Murphy et
al.1997; Xu, Eu et al. 1998).
3.3.4 Reaction with amino acids
The importance of the interaction of NO species with amino acids is exemplified by the
reaction with tyrosine to form 3-nitrotyrosine. This reaction can severely compromise
function of proteins with tyrosine residues in the active site, disrupting structure and activity
@iserich, Patel et al. 1998). This reaction was first described in 1990 (Ohshima, Friesen et al.
1990) and the level of 3-nitrotyrosine is now commonly used diagnostic marker of NO
derived oxidants in both human disease states and animal models (Schmidt, Hofmann et al.
1996). An "overwhelming body of evidence has amassed in the last several years revealing
that NO2Tyr (3-nitrotyrosine) is a reliable footprint of reactive nitrogen species production
that spatially and temporally parallels tissue and cellular injury" @iserich, Patel et al. 1998).
Although a direct relationship between 3-nitrotyrosine formation and pathological outcomes
remains poorly characterised, it is dramatically elevated in diverse diseases such as
atherosclerosis, sepsis, acute and chronic lung disease, neurodegenerative diseases,
inflammatory bowel disease, chronic organ rejection, myocardial inflammation and tobacco
smoking (Ischiropoulos, Zhu et al. 1992; Eiserich, Patel et al. 1998). The compound can be
incorporated into tuberculin which disrupts the cell cytoskeleton @iserich, I{ristova et al.
1998) and can attenuate adrenoreceptor agonists in vivo (Kooy and Royall 1994). The
formation of 3-nitrotyrosine is dependent on increased NO production and frequently
associated with activated phagocytes (neutrophils, monocytes, eosinophils, macrophages). NO
can also interact with amino acid radicals in proteins @iserich, Cross et al. 1996).
3.3.5 Reaction with lipids.
The reactive nitrogen species (NO, NO2, ONOO) also interacts with unsaturated lipids which
leads to either initiation of oxidation, altering the rates and products of lipid oxidation
products or inhibition (see below). For example, the unsaturated free fatty acids arachidonic
acid and linoleate are substrates for the enzymatic synthesis of bioactive medicators such as
prostaglandins and leukotrienes through the activities of lipo-oxygenases, cyclo-oxygenases
and cyochrome Pa56. These play a role in regulation of blood pressure, platelet aggregation,
and bronchosconstriction. Free unsaturated lipids and those esterified to phospholipids are a
significant component to biomembranes pulmonary surfactant and plasma lipoproteins.
Uncontrolled oxidation as can be caused by NO and related species can lead to changes in
integrity and fluidity of biomembranes. The interaction can also lead to the formation of other
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